Methicillin-susceptible Staphylococcus Aureus Bacteremia Research Articles

Meta-meta-analysis of the mortality risk associated with MRSA compared to MSSA bacteraemia.

Staphylococcus aureus bacteraemia (SAB) is a bloodstream infection that carries a high risk of exacerbating a diseased state and may result in an increased death rate. The aim of this study was to assess mortality risk in Methicillin Resistant Staphylococcus aureus (MRSA) bacteraemia compared to Methicillin Susceptible Staphylococcus aureus (MSSA) bacteraemia through meta-meta-analyses. The study followed PRISMA guidelines, conducting a comprehensive search in Scopus, PubMed, and Google Scholar. It included full-text systematic reviews and meta-analyses comparing MRSA vs. MSSA bacteraemia, excluding reviews without data pooling and unclear selection criteria. Validity was assessed using QUOROM and AMSTAR. Edwards' Venn diagrams were used to visualized overlaps between primary studies. Aggregated odds ratio (OR) and risk ratios with 95% confidence intervals were calculated using the random-effect model. Heterogeneity was evaluated using the Higgins I2 statistic. The study included 3 meta-analysis studies, a total of 38,159 patients, with 9,056 having MRSA bacteraemia and 29,103 having MSSA bacteraemia. Data were collected from 46 different outcome studies published between 2001 and 2022. The meta-analyses used 7 to 33 primary studies from 1990 to 2020, with no overlap. Odds ratios (ORs) ranged from 1.78 to 2.92, while relative risks (RR) ranged from 1.57 to 2.37 for the included meta-anlysis. The pooled analysis confirmed a higher risk of mortality in patients with MRSA bacteraemia (OR: 2.35, RR: 2.01, HR: 1.61) compared to MSSA bacteraemia. Heterogeneity among the studies was considerable (I2: 90-91%). The study strongly supports that most patient deaths from SAB are linked to MRSA rather than MSSA. This highlights the significant public health problem posed by SAB, with difficult and often unsuccessful treatment leading to increased mortality and high healthcare costs.

Antistaphylococcal Efficacy of Cefepime, Meropenem, and Piperacillin-Tazobactam in Patients with Polymicrobial Infection with MSSA Bacteremia or Pneumonia

There is a paucity of literature describing de-escalation techniques in patients with polymicrobial infections with one offending organism being methicillin-susceptible Staphylococcus aureus (MSSA) being treated with β-lactam therapy. The purpose of this study is to determine treatment outcomes for patients with polymicrobial infections with MSSA bacteremia or pneumonia who are treated with cefepime (FEP), meropenem (MEM), or piperacillin-tazobactam (TZP). This trial design represents a retrospective observational three-group comparison study of patients at a community teaching hospital system. Patients reviewed included those who had a MSSA bacteremia or pneumonia in addition to a confirmed polymicrobial infection or presence of a coinfection and received definitive therapy with FEP, MEM, or TZP. The primary outcome is defined as the resolution of fever of ≥100.4°F, hypothermia (≤95°F), leukocytosis (WBC °>° 12,000 cells/mm3), and leukopenia with WBC °<° 4,000 cells/mm3. Secondary outcomes included duration of definite therapy, in-hospital mortality, hospital and ICU length of stay (LOS), 30-day readmission rates for a presumed infection, and hospital-acquired Clostridioides difficile infection (HCDI). From August 1, 2016, to August 30, 2019, 45 patients met eligibility criteria. There were no observed differences in primary endpoint ( p = 0.65) or secondary endpoints, i.e., in-hospital mortality ( p = 0.10), hospital LOS ( p = 0.75), ICU LOS ( p = 0.53), 30-day readmission rates for presumed infection ( p = 0.07), or HCDI ( p = 0.34). There was no difference in treatment success with FEP, MEM, or TZP for polymicrobial infections with one offending organism being MSSA. Due to the lack of evidence in this unique patient population and observed results of our study, randomized studies are warranted to determine appropriate therapy in this complex patient population.

248. Evaluation of Continuous versus Intermittent Infusion of Nafcillin in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia

Abstract Background Anti-Staphylococcal penicillins (ASPCN) are first-line agents in the treatment of methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B), and continuous infusion (CI) of oxacillin was associated with higher rates of 30-day microbiological cure versus intermittent (II) in infective endocarditis. Nafcillin (NAF) is the formulary ASPCN at Atrium Health (AH) and is variably ordered as CI or II. The purpose of this study is to compare NAF infusion strategies and related outcomes in the treatment of MSSA-B. Methods This was a retrospective, observational, multisite study at 15 sites in the Greater Charlotte, NC Region of AH. Hospitalized adults with MSSA-B who received NAF from 1/1/2020 – 3/31/2022 were included. The primary outcome was receipt of CI vs II NAF. Secondary outcomes included time to microbiological cure (TTMIC), in-hospital 30-day all-cause mortality, hospital length of stay (LOS), and rates of adverse drug events (ADE) - acute kidney injury (serum creatinine increase at least 1.5 times baseline), transaminitis (aspartate aminotransferase / alanine transaminase ≥ 5 times the upper limit of normal), hypokalemia (potassium of ≤ 2.9 mmol/L), and allergic reaction. TTMIC, in-hospital mortality, LOS, and ADEs were also evaluated in a cohort of patients in the ICU within 48 hours of NAF start. Results A total of 166 patients were included: 99 (59.6%) in the CI group and 67 (40.4%) in the II group. Thirteen patients in the II group were eventually changed to CI, but their results were analyzed in the II group. TTMIC was not significantly different between the CI and II group (5 vs 4 days, respectively p = 0.56), with similar time to receipt of NAF in both groups (Figure 1). In-hospital mortality, hospital LOS, and rates of ADE also did not differ between groups (Figure 1). Forty-seven patients were included in the ICU cohort: 29 in the CI group and 18 in the II group. Trends observed in the ICU cohort were similar to those observed in the larger population (Figure 2).Table 1.Selected Baseline Characteristics Figure 1 Figure 2 Conclusion In a small, unmatched, observational cohort of patients with MSSA-B, outcomes were not different based on NAF administration route. This suggests that administration strategy should be determined based on patient specific factors, such as available lines and patient convenience. Disclosures All Authors: No reported disclosures

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP) Bloodstream Infection Annual Report 2022.

From 1 January to 31 December 2022, fifty-five institutions across Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP). The aim of ASSOP 2022 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 3,214 SAB episodes were reported, of which 77.5% were community-onset. Overall, 15.0% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 21.4%, which was significantly different to the 16.8% all-cause mortality associated with methicillin-susceptible SAB (p = 0.02). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 31% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 13% to tetracycline; 11% to gentamicin; and 2% to co-trimoxazole. One MRSA isolate, with a daptomycin MIC of 1.5 mg/L, harboured the A302V mprF and A23V cls2 mutations. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in one MRSA isolate. Resistance to vancomycin or linezolid was not detected. Resistance to non-β-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and to the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired resistance to multiple antimicrobials including ciprofloxacin, clindamycin, erythromycin, gentamicin, and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 86% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 72% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST97-IV [2B]; ST953-IV [2B]; and ST8-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III–IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), –5.95–16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345.

Daptomycin Plus Oxacillin for Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia.

The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection. We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB. This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation. Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively. D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB.

Early switching from intravenous to oral antibiotic therapy in bone and joint infections associated with methicillin-susceptible Staphylococcus aureus bacteremia

ObjectivesWe aimed to evaluate the clinical outcomes of patients with bone and joint infection (BJI) associated with methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) treated with early oral switch to oral antibiotics (before day 14) versus later or no switch. Patients and methodsWe included all cases reported between January 2016 and December 2021 in the University Hospital of Reims. ResultsAmong 79 patients with BJI associated with MSSAB, 50.6% had an early switch to oral antibiotics, with median duration of intravenous antibiotics of 9 (IQR 6–11) days. The overall cure rate was 81% with follow-up of 6 months, and was 85.7% after excluding the 9 patients whose death was not related to BJI infection. Failure to control BJI did not differ between the two groups. ConclusionAn early (before day 14) switch to oral antibiotics may be a safe therapeutic option in BJI associated with MSSAB.

Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment

IntroductionA major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce...

Retrospective Evaluation of the Association of Oxacillin MIC on Acute Treatment Outcomes with Cefazolin and Antistaphylococcal Penicillins in Methicillin-Susceptible Staphylococcus aureus Bacteremia.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Therapeutic Options for Adult Patients With Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Narrative Review.

To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. A literature search using the PubMed database (inception to December 2022) was conducted using the search terms "Staphylococcus aureus bacteremia," "methicillin-susceptible Staphylococcus aureus bacteremia," "persistent methicillin-susceptible Staphylococcus aureus bacteremia," and "refractory methicillin-susceptible Staphylococcus aureus bacteremia ." In addition, therapeutic agents which could be used as treatment for MSSA including "nafcillin," "oxacillin," "cefazolin," "ceftaroline," "gentamicin," "rifampin," and "daptomycin" were also combined with the aforementioned search terms to capture data using these agents. Clinical data were limited to those published in the English language. Articles and abstracts were considered for inclusion in addition to ongoing trials identified through ClinicalTrials.gov. A total of 78 articles were reviewed including 17 in vitro or animal model studies and 39 studies including patient data. The remaining 22 articles included guidelines, review articles, and editorials. Recent data evaluating use of dual β-lactam regimens for persistent MSSA bacteremia were limited to 8 case reports or case series. At present, there is little guidance on how to best manage patients with persistent MSSA bacteremia. This narrative review collates the available data to assist clinicians in selecting the best possible antimicrobial regimen when facing this clinical conundrum. Modification of antimicrobial therapy, in conjunction with source control and infectious diseases consultation, may all be necessary to sterilize blood cultures in patients with persistent MSSA bacteremia.

Disseminating MSSA Infection in a Preterm Infant With Rare Finding of Spinal Epidural Abscess: A Case Report.

Methicillin-susceptible Staphylococcus aureus (MSSA) occurs more frequently in the neonatal intensive care unit (NICU) than methicillin-resistant S. aureus (MRSA) and can result in comparable morbidity and mortality in the neonatal population. MSSA infection may present as pustulosis or cellulitis and evolve into bacteremia, pneumonia, endocarditis, brain abscesses, and osteomyelitis. There is a paucity of literature regarding the treatment and long-term outcomes in the premature infant. A 32-week twin developed MSSA sepsis with presentation of pain, decreased movement of upper extremities, and global hypotonia. Blood cultures remained positive despite antibiotic coverage. The infant was admitted to the level IV NICU with the diagnosis of MSSA bacteremia, with concern for dissemination and osteomyelitis. Diagnostic studies included laboratory testing for sepsis evaluation, radiologic studies to evaluate for dissemination, immunologic testing to rule out complement deficiency, and hematology testing to rule out hypercoagulable conditions. Diagnostic testing showed extensive cellulitis, osteomyelitis, multiple liver abscesses, and epidural abscesses suggestive of spinal epidural abscess (SEA). Abscess debridement and irrigation on the left distal femur, left elbow, and right tibia were performed. The infant completed 8 weeks of IV antibiotic therapy. Immunologic and hematology testing was within normal limits. Prompt recognition and follow-up for clinical signs of sepsis are vital when caring for premature infants. Inclusion of pediatric subspecialist recommendations to assure all diagnostic studies and treatments are completed can significantly impact the patient's outcome. Long-term follow-up is needed for premature infants with the diagnosis of SEA.

Microbiological and Clinical Outcomes of Methicillin-Susceptible Staphylococcus aureus Isolated in Lung Transplant Perioperative Donor and Recipient Respiratory Cultures.

Staphylococcus aureus is one of the most common organisms isolated from respiratory secretions in lung transplant donors and recipients perioperatively. Within the first 90 days after lung transplantation, methicillin-susceptible Staphylococcus aureus (MSSA) infections have been associated with increased mortality and acute and chronic rejection. However, it is unclear whether respiratory cultures positive for MSSA at the time of transplantation can lead to clinically significant infection. The aim of this study was to assess the microbiological and clinical outcomes for lung transplant recipients (LTRs) with positive perioperative donor or/and recipient respiratory cultures for MSSA. A retrospective study was conducted evaluating MSSA-positive respiratory cultures at the time of lung transplantation from donors and/or recipients from January 1, 2008, to December 30, 2019. Patients who did not have a bronchoalveolar lavage at 2 weeks after the lung transplant or died within 2 weeks of lung transplant were excluded. The main outcome was MSSA eradication at 2-week bronchoscopy. Recipients were evaluated for MSSA infections at the 12-week period after the transplant. Of the 1,678 individuals who underwent lung transplantation, 218 LTRs had S. aureus isolated in perioperative donor or recipient respiratory cultures, and 29 were subsequently excluded. Of the remaining 189 LTRs, MSSA eradication at the 2-week bronchoscopy was achieved in 186 (98.4%) recipients. During the 12-week follow-up, 15 (7.9%) recipients were diagnosed with MSSA pneumonia; concurrent MSSA bacteremia was noted in one recipient. No anastomotic infection, empyema, or lung abscess related to MSSA was diagnosed during the follow-up period.In LTRs, the rate of MSSA eradication at 2-week post-transplant recipients is high, and it is associated with a low rate of infectious complication within the first 12 weeks after transplant. Most of the recipients received a combination therapy with at least one agent active against MSSA. More studies to evaluate the optimal antimicrobial stewardship policies regarding the regimen and duration of antibiotic therapy for these patients are needed.

432: EFFICACY OF TARGETED VS. NONTARGETED BETA-LACTAM THERAPY FOR MSSA BACTEREMIA: A MATCHED COHORT STUDY

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) is implicated in blood stream infections with high morbidity and mortality. Targeted treatment (TT) with nafcillin or cefazolin is considered first-line therapy, however patients may receive broad spectrum therapy for MSSA bacteremia for various reasons. We hypothesize non-targeted beta-lactams (NT) are less effective for blood culture clearance compared to TT for MSSA bacteremia. Methods: Critically ill patients >18 years old with an MSSA positive blood culture between 7/1/2014 and 12/31/2020 were included. Patients were identified retrospectively through the electronic medical record and must have received either a NT (ampicillin/sulbactam, ceftriaxone, cefepime, piperacillin/tazobactam, meropenem) or TT. The TT cohort included the receipt of or de-escalation to nafcillin or cefazolin within 72 hours of antibiotic initiation. Patients with lack of follow-up blood cultures, death, or discharge within 48 hours of positive culture were excluded. Patients were matched according to age, Charlson Comorbidity Index (CCI), presence of a central line, and source of bacteremia. The primary outcome was duration of bacteremia. Secondary outcomes included hospital and intensive care unit (ICU) length of stay (LOS) and inpatient mortality. Results: Of 423 patients, 178 were included based on matching criteria. The majority of patients were male (63%) and Caucasian (92%) with a median age of 56 (interquartile range [IQR], 47-65). Median CCI was 5 in both groups (IQR, 3-8). The most frequent NT were piperacillin/tazobactam (56%) and cefepime (34%). There was no significant difference in duration of bacteremia (3.4 vs 3.4 days, p=0.653), hospital LOS (18.9 vs 26.4 days, p=0.071), or ICU LOS (5.3 vs 5.9 days, p=0.966) in the TT vs NT cohorts, respectively. Patients in the TT cohort had significantly lower mortality compared to those in the NT cohort (12.4% vs 24.7%, p=0.034). Conclusions: ICU patients who received TT or NT had similar duration of bacteremia, hospital LOS, and ICU LOS. Exposure to NT was associated with increased mortality. Although these results should be validated prospectively, clinicians should be cognizant of this risk when evaluating those with MSSA bacteremia and consider de-escalation to TT as soon as clinically appropriate.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP).

From 1 January to 31 December 2021, forty-eight institutions around Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Programme (ASSOP). The aim of ASSOP 2021 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 2,928 SAB episodes were reported, of which 78.4% were community-onset. Overall, 16.9% of S. aureus isolates were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 15.0%, which was not significantly different from the 14.4% all-cause mortality associated with methicillin-susceptible SAB (p = 0.7). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 36% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 15% to tetracycline; 16% to gentamicin; and 3% to co-trimoxazole. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in three S. aureus isolates. Resistance to vancomycin or linezolid was not detected. Resistance to non-β-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 85% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 68% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST45-V [5C2&5]; ST5-IV [2B]; ST1-IV [2B]; ST30-IV [2B]; and ST97-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia.

Ceftriaxone versus cefazolin for the treatment of methicillin-susceptible Staphylococcus aureus bacteraemia

Few studies have evaluated the use of ceftriaxone (CRO) in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. The purpose of this study was to compare the safety and efficacy of CRO versus cefazolin (CZO) for patients with MSSA bacteraemia. This was a multicentre, single health-system, retrospective study. Adult inpatients were included if they had a primary episode of MSSA bacteraemia and received CRO or CZO as definitive therapy. The primary endpoint was clinical cure at 28 days or at discharge, whichever came first. Secondary endpoints included treatment failure at 90 days, time to treatment failure, re-admission due to recurrent MSSA bacteraemia, duration of bacteraemia, discontinuation of treatment due to adverse drug events, and Clostridioides difficile infection. A total of 248 patients were included, of which 87 (35.1%) received CRO and 161 (64.9%) received CZO. There was no difference in the primary outcome of clinical cure at 28 days or at discharge between the CRO and CZO groups [75 (86.2%) vs. 145 (90.1%); P=0.359], even after adjusting for Charlson comorbidity index and Pitt bacteremia score (adjusted OR=1.35, 95% CI 0.58-3.12; P=0.49). There were no differences in time to clinical cure, treatment failure at 90 days or safety events between the two groups. In conclusion, our findings suggest no clinical difference between CRO and CZO for the definitive treatment of MSSA bacteraemia. Further prospective studies are needed to confirm these findings.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2020.

From 1 January to 31 December 2020, forty-nine institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aims of ASSOP 2020 were to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin; and to characterise the molecular epidemiology of the methicillin-resistant isolates. A total of 2,734 SAB episodes were reported, of which 79.7% were community-onset. Of S. aureus isolates, 17.6% were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 14.2%, which was not significantly different from the 13.3% mortality associated with methicillin-susceptible SAB (p = 0.6). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 35% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin, 33% to ciprofloxacin, 13% to tetracycline, 13% to gentamicin and 4% to co-trimoxazole. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in four S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA (HA-MRSA) clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. However, 85% percent of methicillin-resistant SAB isolates were community-associated MRSA (CA-MRSA) clones. Although polyclonal, approximately 77% of CA-MRSA clones were characterised as: ST93-IV [2B] (Queensland CA-MRSA); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST8-IV [2B]; and ST97-IV [2B]. The CA-MRSA clones, in particular ST45-V [5C2&5], have acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The multi-resistant ST45-V [5C2&5] clone accounted for 11.0% of CA-MRSA. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus sepsis.

Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia.

ABSTRACTOur objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables.IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.

72. Evaluation of Acclerate Pheno™ on Clinical and Antimicrobial Outcomes in Patients with Methicillin Susceptible Staphylococcus aureus Bloodstream Infections

BackgroundAnti-staphylococcal beta-lactams (BL) are treatment of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) as they have superior MSSA bacteremia clearance. Based on the hypothesis that earlier initiation of anti-staphylococcal BL may improve clinical outcomes, this study compared clinical and microbiologic features of patients with MSSA BSI pre- and post-implementation of Accelerate Pheno™ (AXDX).MethodsThis was a case-control analysis of adult inpatients with MSSA BSI analyzed using AXDX compared to traditional laboratory methods. Cases were prospectively identified by the antimicrobial stewardship team between August and October 2020 post implementation of AXDX in July 2020. Patients were matched with historical controls (July 2018–July 2020) based on age (±4 years), gender, organism, and source of infection. The primary outcome was time to antibiotic (abx) deescalation to an anti-staphylococcal beta-lactam. Secondary outcomes included hospital length of stay (LOS), 30-day all-cause mortality and hospital readmission, and 60-day C. difficile infection.ResultsA total of 25 cases with MSSA BSI were identified, of which 18 (72%) were matched to historical controls. Of these patients, 12 (67%) were male with an average age of 67 years (SD ±12). Other demographics were similar between groups. The median time to species identification [21.3 hours in cases (IQR 14–31.9) vs 33.3 hours in controls (29–41.7), p=0.046] and abx susceptibilities [22.5 hours (18.8 – 42) vs 60.1 hours (46–61.9), p< 0.001] were significantly shorter in cases. The average time to abx deescalation from time to organism susceptibility was 1.7 days (±1.9) for cases compared to 2.7 days (±1.5) for controls (p = 0.129). There were no significant differences detected in hospital LOS, 30-day mortality or readmission, and 60-day C.difficile infection.ConclusionAlthough time to organism identification and abx susceptibilities was significantly shorter in cases, AXDX was not associated with a statistically significant reduction in time to anti-staphylococcal BL initiation nor a difference in associated clinical outcomes. A trend in shorter time to abx de-escalation was observed and warrants further investigation in a larger population.Disclosures All Authors: No reported disclosures

Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital.

Cefazolin is an essential antibiotic used for treating bacteremia; in particular, it is recommended as a first-line agent for infections caused by methicillin-susceptible Staphylococcus aureus (MSSA). In March 2019, problems with a major antibiotic supplier caused a critical shortage of cefazolin in Japan; however, the impact of the cefazolin shortage on clinical outcomes remains unknown. This study aimed to evaluate the effect of the cefazolin shortage in patients with MSSA bacteremia. Data from 75 patients were compared between the pre-shortage (March 2018–January 2019, n = 39) and post-shortage (March 2019–January 2020, n = 36) periods. There were no significant differences in the demographic characteristics between the two groups, and the cefazolin shortage did not worsen clinical outcomes such as adverse drug reactions, treatment failure, and 30-day mortality. In the post-shortage group, ampicillin/sulbactam and benzylpenicillin were more frequently administered as alternative antibiotics for empirical and definitive therapy (10% vs. 31%, p = 0.042; 0% vs. 19%, p = 0.004, respectively). Multivariate analysis revealed that the broad-spectrum antibiotics for definitive therapy, such as antipseudomonal penicillin, were associated with treatment failure in patients with MSSA bacteremia (OR = 17, p = 0.003). Hence, narrow-spectrum antibiotics should be prescribed for MSSA bacteremia as alternatives during a cefazolin shortage.

Impact of agr Functionality on the Outcome of Patients with Methicillin-Susceptible Staphylococcus aureus Bacteremia.

ABSTRACTDysfunctional accessory gene regulator (agr) is associated with unfavorable outcomes in invasive methicillin-resistant Staphylococcus aureus infections. However, it is unknown whether this association persists in methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B). This study evaluated the association between agr dysfunction and mortality in patients with MSSA-B. This retrospective cohort study included MSSA-B patients (≥15 years) enrolled from June 2014 to June 2019 and retrospectively collected their demographic and clinical information. Stored causative strains were measured for agr functionality by δ-hemolysin production assays. Among 244 MSSA-B patients, 91 (37.3%) and 153 (62.7%) had dysfunctional and functional agr MSSA-B, respectively. Ninety-day mortality occurred in 18.7% and 17.6% dysfunctional and functional groups, respectively (P = 0.97). Kaplan-Meier analysis showed that mortality due to dysfunctional agr MSSA-B was not significantly higher (P = 0.82). Age, sites, the severity of infection, and comorbidity adjusted hazard ratio (aHR) of the dysfunctional group for 90-day mortality was 1.303 (95% confidence interval [CI], 0.698 to 2.436, P = 0.41). Mortality due to MSSA-B with sequential organ failure assessment (SOFA) scores of 2 to 5 was significantly higher in the dysfunctional group (P = 0.03), and the dysfunctional agr aHR for 90-day mortality was 3.260 (95% CI, 1.050 to 10.118, P = 0.04). The agr dysfunction of causative organisms can have a significant effect on the outcomes of MSSA-B in patients with moderate severity (SOFA scores 2 to 5).IMPORTANCE Few studies have examined the association between methicillin-susceptible Staphylococcus aureus (MSSA) infection and accessory gene regulator (agr) functionality. We evaluated the association between agr dysfunction and mortality in patients with MSSA bacteremia. Dysfunctional agr is associated with lower survival in MSSA bacteremia patients with moderately severe sequential organ failure assessment (SOFA) scores of 2 to 5. We found that the agr functionality of causative organisms may have an effect on patients’ outcomes in MSSA like in methicillin-resistant S. aureus.